Phenotypes Associated with This Genotype

Genotype
MGI:3850502

• Allelic Composition: Tg(Lck-Tslp)1Chea/0
• Genetic Background: B6.Cg-Tg(Lck-Tslp)1Chea

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

immune system

enlarged spleen ( J:72982 )

• mice exhibit pronounced spleen hypertrophy compared with wild-type mice

• however, cellular architecture is preserved

increased spleen weight ( J:72982 )

• average spleen weight is ~5x that of wild-type controls

increased immunoglobulin level ( J:72982 )

• most mice exhibit cryoglobulins positive for IgG1, IgM, and kappa and lambda chains

• mice develop polyclonal mixed cryoglobulinemia

enlarged lymph nodes ( J:72982 )

increased anti-nuclear antigen antibody level ( J:72982 )

• in 11 of 25 mice

liver inflammation ( J:72982 )

glomerulonephritis ( J:72982 )

• mice develop cryoglobulinemic membranoproliferative type glomerulonephritis that is more severe in female mice than in male mice

lung inflammation ( J:72982 )

• lungs exhibit perivascular leukocyte infiltration unlike in wild-type mice

• lung inflammation becomes severe

renal/urinary system

abnormal glomerular capillary morphology ( J:72982 )

• capillary walls are thickened, sometimes with prominent double contours of the capillary walls

• PAS-positive deposits detected in capillary walls, leading to intracapillary globular thrombi and complete capillary occlusion in severe cases

• number of patent capillary lumina decreases as diseases progresses

• subendothelial deposits, cellular interposition and splitting of capillary walls

• leukocytes found in capillary lumina, some adhering to endothelial cells, others infiltrating the mesangium

• however, no leukocytic infiltrates are detected in arterial walls

abnormal glomerular capillary endothelium morphology ( J:72982 )

• endothelial cells covering the immune deposits show signs of activation, with cellular swelling and absence of normal pores

abnormal glomerular endothelium fenestra morphology ( J:72982 )

• endothelial cells covering the immune deposits lack normal pores

albuminuria ( J:72982 )

• significant increase in albumin excretion in both sexes; the albumin to creatinine ratio is increased 2.5-fold in male mice and 5-fold in female mice compared to in wild-type mice

glomerulonephritis ( J:72982 )

• mice develop cryoglobulinemic membranoproliferative type glomerulonephritis that is more severe in female mice than in male mice

podocyte foot process effacement ( J:72982 )

• seen in areas of capillary walls involved by immune deposits

abnormal glomerular mesangium morphology ( J:72982 )

• both sexes show widening of the mesangial area at 1 month of age; due to an increase in mesangial matrix and mesangial deposits of immune complexes

• PAS-positive deposits detected in the mesangium

mesangial cell interposition ( J:72982 )

expanded mesangial matrix ( J:72982 )

• increase in mesangial matrix at >1 month of age

• more prominent in females at early time points (1 to 2 months of age) than in males

increased renal glomerulus lobularity ( J:72982 )

• increased glomerular size with an absolute increase in the cell number per glomerulus

• accentuated lobular appearance of the glomerular tuft architecture is often observed

• however, globally sclerotic glomeruli are absent and the tubulointerstitium remains unaffected with no significant inflammation or fibrosis

renal glomerular immunoglobulin deposits ( J:72982 )

• glomeruli exhibit expansion of the mesangium due to increased matrix and accumulation of immuno-deposits, subendothelial immune-deposits, focal occlusion of capillary loops, and monocyte/macrophage influx unlike in wild-type mice

respiratory system

increased lung weight ( J:72982 )

lung inflammation ( J:72982 )

• lungs exhibit perivascular leukocyte infiltration unlike in wild-type mice

• lung inflammation becomes severe

cardiovascular system

abnormal glomerular capillary morphology ( J:72982 )

• capillary walls are thickened, sometimes with prominent double contours of the capillary walls

• PAS-positive deposits detected in capillary walls, leading to intracapillary globular thrombi and complete capillary occlusion in severe cases

• number of patent capillary lumina decreases as diseases progresses

• subendothelial deposits, cellular interposition and splitting of capillary walls

• leukocytes found in capillary lumina, some adhering to endothelial cells, others infiltrating the mesangium

• however, no leukocytic infiltrates are detected in arterial walls

abnormal glomerular capillary endothelium morphology ( J:72982 )

• endothelial cells covering the immune deposits show signs of activation, with cellular swelling and absence of normal pores

abnormal glomerular endothelium fenestra morphology ( J:72982 )

• endothelial cells covering the immune deposits lack normal pores

enlarged heart ( J:72982 )

• in some mice

growth/size/body

enlarged heart ( J:72982 )

• in some mice

decreased body weight ( J:72982 )

• in female mice

increased lung weight ( J:72982 )

increased liver weight ( J:72982 )

enlarged spleen ( J:72982 )

• mice exhibit pronounced spleen hypertrophy compared with wild-type mice

• however, cellular architecture is preserved

increased spleen weight ( J:72982 )

• average spleen weight is ~5x that of wild-type controls

homeostasis/metabolism

increased blood urea nitrogen level ( J:72982 )

• small but significant increase in blood urea nitrogen in both sexes

abnormal glomerular capillary thrombosis ( J:72982 )

• PAS-positive deposits detected in capillary walls, leading to intracapillary globular thrombi and complete capillary occlusion in severe cases

albuminuria ( J:72982 )

• significant increase in albumin excretion in both sexes; the albumin to creatinine ratio is increased 2.5-fold in male mice and 5-fold in female mice compared to in wild-type mice

hematopoietic system

enlarged spleen ( J:72982 )

• mice exhibit pronounced spleen hypertrophy compared with wild-type mice

• however, cellular architecture is preserved

increased spleen weight ( J:72982 )

• average spleen weight is ~5x that of wild-type controls

increased immunoglobulin level ( J:72982 )

• most mice exhibit cryoglobulins positive for IgG1, IgM, and kappa and lambda chains

• mice develop polyclonal mixed cryoglobulinemia

liver/biliary system

increased liver weight ( J:72982 )

liver inflammation ( J:72982 )

integument

spontaneous skin ulceration ( J:72982 )

• 22% of male and 4% of female mice develop progressive ulcerative lesions of the ears

cellular

mesangial cell interposition ( J:72982 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cryoglobulinemia		DOID:2917		J:72982
membranoproliferative glomerulonephritis		DOID:2920	OMIM:305800	J:72982